PMID- 17932230
OWN - NLM
STAT- MEDLINE
DCOM- 20080206
LR  - 20211020
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 293
IP  - 6
DP  - 2007 Dec
TI  - The proinflammatory phenotype of PECAM-1-deficient mice results in atherogenic 
      diet-induced steatohepatitis.
PG  - G1205-14
AB  - The severity of nonalcoholic steatohepatitis (NASH) is determined by 
      environmental and genetic factors, the latter of which are incompletely 
      characterized. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 
      130-kDa transmembrane glycoprotein expressed on blood and vascular cells. In the 
      present study, we provide data for the novel finding that genetic deficiency of 
      PECAM-1 potentiates the development and progression of NASH. We found that the 
      rate of development and severity of diet-induced NASH are markedly enhanced in 
      PECAM-1-deficient [knockout (KO)] mice relative to wild-type (WT) mice, as 
      measured by histological and biochemical evaluation. Livers from KO mice 
      exhibited typical histological features of NASH, including macrovesicular fat 
      accumulation, hepatocyte injury with infiltration of inflammatory cells, 
      fibrosis, and heightened oxidative stress. Alanine aminotransferase, a marker for 
      liver injury, was also significantly higher in KO compared with WT mice. 
      Consistent with a role for PECAM-1 as a suppressor of proinflammatory cytokines, 
      plasma levels of inflammatory cytokines, including TNF-alpha and monocyte 
      chemoattractant protein-1 (MCP-1), were also significantly higher in KO compared 
      with WT mice. These findings are the first to show that the PECAM-1-deficient 
      mouse develops progressive nonalcoholic fatty liver disease (NAFLD), supporting a 
      role for PECAM-1 as a negative regulator of NAFLD progression. Future examination 
      of recently identified PECAM-1 allelic isoforms in humans as potential risk 
      factors for developing NASH may be warranted.
FAU - Goel, Reema
AU  - Goel R
AD  - Blood Research Institute, BloodCenter of Wisconsin, P.O. Box 2178, Milwaukee, WI 
      53201, USA. reema.goel@bcw.edu
FAU - Boylan, Brian
AU  - Boylan B
FAU - Gruman, Lynn
AU  - Gruman L
FAU - Newman, Peter J
AU  - Newman PJ
FAU - North, Paula E
AU  - North PE
FAU - Newman, Debra K
AU  - Newman DK
LA  - eng
GR  - R01 HL090883/HL/NHLBI NIH HHS/United States
GR  - HL-40926/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071011
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Immunologic Factors)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*metabolism/*pathology
MH  - *Diet, Atherogenic
MH  - Hepatitis/*metabolism/*pathology
MH  - Immunologic Factors/metabolism
MH  - Liver/*metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phenotype
MH  - Platelet Endothelial Cell Adhesion Molecule-1/genetics/*metabolism
MH  - Steatitis/metabolism/pathology
EDAT- 2007/10/13 09:00
MHDA- 2008/02/07 09:00
CRDT- 2007/10/13 09:00
PHST- 2007/10/13 09:00 [pubmed]
PHST- 2008/02/07 09:00 [medline]
PHST- 2007/10/13 09:00 [entrez]
AID - 00157.2007 [pii]
AID - 10.1152/ajpgi.00157.2007 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1205-14. doi: 
      10.1152/ajpgi.00157.2007. Epub 2007 Oct 11.